Novel Drug for Diabetes and Cardiovascular Disease Advanced by Ligand/Lilly Alliance; Ligand Receives Milestone from Lilly for New Generation of Insulin-Sensitizer.

Business Editors & Health/Medical Writers

BIOWIRE2K

SAN DIEGO--(BW HealthWire)--Oct. 4, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced today that LY510929, a novel PPAR agonist, and a back-up compound have been declared clinical candidates for development as novel oral treatments for type 2 diabetes and cardiovascular disease.

Ligand expects an Investigational New Drug Application (IND) to be filed with the FDA for LY510929 or the back-up compound in the second half of 2001. Ligand received undisclosed milestone payments from Eli Lilly and Company (NYSE:LLY) and may receive additional milestone payments should any compound progress through human development.

LY510929 is one of several advanced RXR and PPAR modulators being pursued under a five-year collaboration entered into in November 1997 between Lilly and Ligand. The collaboration focuses on the discovery and development of drugs with broad applications across metabolic diseases, including type 2 diabetes, obesity, dyslipidemia, cardiovascular disease associated with insulin resistance and obesity. Ligand technology forms the basis of the discovery effort targeting nuclear hormone receptors including the PPAR/RXR heterodimer, HNF-4, and the ob gene. Lilly is responsible for the development and registration of any products resulting from the collaboration. Lilly has exclusive worldwide marketing rights to products resulting from the research and will pay Ligand royalties on sales of such products if commercialized.

"Lilly and Ligand embarked on a major strategic alliance to develop novel oral therapies for the treatment of type 2 diabetes, obesity and associated cardiovascular disorders," said David E. Robinson, Ligand Chairman, President and CEO. "We are extremely pleased today that this program has produced the first clinical candidate and back-up in what we hope will be a steady stream of novel oral small molecules addressing the growing and unmet needs of diabetic and obese patients. These compounds further expand our growing pipeline of products on human development track for diabetes, cardiovascular disease and dyslipidemia, which increase our potential for future milestone and royalty revenues."

"This novel PPAR co-agonist is one of an emerging new class of insulin sensitizers and lipid regulators with enhanced potential in the treatment of type 2 diabetes (NIDDM), which affects the health of over 15 million Americans, and cardiovascular disease, the leading cause of death in industrialized countries," said Andres Negro-Vilar, M.D., Ph.D., Ligand Senior Vice President of Research and Development and Chief Scientific Officer. "Low levels of HDL (good) cholesterol and high levels of LDL and triglycerides are powerful risk factors for the development of cardiovascular disease; type 2 diabetes is often associated with these disorders of cholesterol and triglyceride metabolism. Preclinical data suggests that LY510929 may offer patients both better control of blood glucose and reduction in risk factors for cardiovascular disease by increasing HDL while lowering triglycerides and LDL cholesterol. It is the first of multiple compounds with differing selective receptor profiles (RXR and PPAR) that are advancing toward human development track in 2000 and 2001 and are targeted to be 'best in class' upon market entry."

Diabetes and Cardiovascular Disease

Diabetes is an incurable chronic disease in which the body does not produce or properly use insulin, a hormone that is needed to convert sugar, starches, and other food into energy. According to the American Diabetes Association, 15.7 million people in the United States have diabetes; 5.4 million are undiagnosed. Approximately 800,000 individuals will be diagnosed with diabetes this year. Diabetes is the sixth leading cause of death by disease in the United States. Diabetic patients have a greatly increased risk of heart disease as well as blindness, kidney failure and limb amputation.

Cardiovascular disease, the leading cause of death in industrialized countries, affects more than 58 million Americans, nearly 14 million of whom have coronary heart disease. According to the World Health Organization (WHO), worldwide cardiovascular disease kills more people than any other disease, accounting for at least 15 million deaths, or 30% of all deaths, every year. Many millions more are disabled by the disease.

Ligand Pharmaceuticals Incorporated

Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, skin diseases, and men's and women's hormone-related diseases, as well as osteoporosis, metabolic disorders and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs) and Signal Transducers and Activators of Transcription (STATs). Additional information about Ligand is available at http://www.ligand.com.

Ligand Pharmaceuticals' releases are available on the World Wide Web at www.businesswire.com/cnn/lgnd.htm.

This news release may contain certain forward-looking statements by Ligand which involve risks and uncertainties and reflect Ligand's judgement as of the date of this release. Actual events or results may differ from Ligand's expectations. There can be no assurance that results of clinical studies of LY510929 or any other compound in the Lilly/Ligand collaboration will confirm pre-clinical results or that LY510929 or any other such compound will advance to clinical trials or will prove effective in treating diabetes, cardiovascular disease or any other disease. Additional information concerning these and other risk factors affecting Ligand's business can be found in prior press releases as well as in public periodic filings with the Securities and Exchange Commission. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.